Oxidation of mixed tar bases



United States Patent OXIDATION OF MIXED TAR BASES Robert S. Barker and Robert H. Ebel, Plainfield, N. 1., assignors to American Cyanamid Company, New York, N. Y., a corporation of Maine No Drawing. Application September 26, 1952, Serial No. 311,776

2 Claims. (Cl. 260-295) This invention relates to an improved process of-preparing isonicotinic acid.

In the past, isonicotinic acid has been obtained by the oxidation, for example, with mixed nitric and sulfuric acids of gamma picolines. This necessitates obtaining gamma picoline which does not occur except in admixture with beta picoline forming the so-called mixed picoline fraction in the distillation of coal tar bases. The two compounds which are usually accompanied by a small amount of 2,6-lutidine cannot be practically separated by ordinary distillation means. As a result, gamma picoline has been relatively expensive which has increased the cost of the isonicotinic acid. The present invention involves a simple method in which a derivative of gamma picoline, namely, the reaction product of gamma picoline with formaldehyde is oxidized. Formaldehyde is known to react with gamma picoline and it is possible to produce three products having one, two or three methylol groups attached to the 4-methyl group of the gamma picoline. The methylolated gamma picolines so obtained may be represented by the following generic formula (HhrQ-(CH OH) 11 wherein n is an integer from 1 to 3 and m is 3n. In the past only the monomethylol derivative, 4-beta-hydroxyethyl pyridine, has been desired because this can be dehydrated to 4-vinyl pyridine for which there was a considerable market in the synthetic fiber industry. Every effort was made to prevent the formation of the diand trimethylol derivatives. According to the present invention, any of the formaldehyde reaction products is oxidized directly to isonicotinic acid, the additional methylol groups doing no harm except to consume some additional oxidizing agent. It is therefore possible to carry out the reaction of formaldehyde with mixed picolines to produce a large proportion of methylolated gamma picoline without regard to whether it is all the monomethylol derivative. This product can either be separated from the beta picoline which does not react with formaldehyde or the mixture may be used as such in the oxidation reaction. It has been found that the methylolated gamma picolines are much more readily oxidized than the unmethylolated derivatives or than beta picoline. In fact, the oxidation proceeds so readily that it can be effected with nitric acid alone without using any sulfuric acid or sulfur trioxide. The much milder oxidation procedure permits the preferred embodiment of the present invention in which the crude reaction mixture of formaldehyde and mixed picolines, if desired after removing water, can be oxidized under mild conditions, for example, with nitric acid alone or with mixed acids under lower temperatures so that isonicotinic acid is produced without substantial oxidation of the accompanying beta picoline. This is a very efficient process because the unreacted beta picoline can be easily recovered by steam distillation or other means and is then present in a form in which it can be directly oxidized to nicotinic acid for which there is a large market in the vitamin field. The presence of small amounts of 2,6-. lutidine do not interfere even though they form methylol derivatives, since the resultant carboxylic acid is easily separated from isonicotinic acid because of a large difference in water solubility. In other words, the preferred embodiment of the present invention permits the economical production without additional separation steps of both isonicotinic acid and nicotinic acid in high grade suitable for pharmaceutical use.

As has been pointed out above, it is possible to separate the methylolated gamma picoline from the unmethylolated beta picoline and where desired, this may be done. In other words, the present invention includes the oxidation of the methylolated gamma picoline even though it has no beta picoline associated with it. In such a case, the advantages of easier oxidation are obtained but there is sacrificed the additional advantage of the saving of the separation step which is the reason that the oxidation of the formaldehyde-reacted mixed picolines constitutes a preferred embodiment of the present invention.

The invention presents the advantage that the oxidation of the methylolated gamma picolines can be effected under conditions sufficiently mild so that beta picoline is substantially unoxidized. It is, of course, possible to use more drastic means with higher temperatures and mixed acids containing oleum with or without a catalyst, such as ferric bromide, and oxidize the methylolated derivatives in good yield to a high-grade product. However, the use of these more drastic means when the beta picoline has not been removed results in a mixture of nicotinic and isonicotinic acids which have to be separated. This separation is not too difficult because of recent discoveries, but it is still usually more expensive than the simple steam distillation of unreacted beta picoline. While the invention therefore includes processes of oxidation which are sufiiciently drastic to oxidize beta picoline in its preferred embodiment, the additional advantages of the cheaper separation of beta picoline in unreacted form constitutes an important economic advantage.

The invention will be described in greater detail in conjunction with the following specific examples in which the parts are by weight unless otherwise specified.

Example 1 Forty-five parts of mixed picolines containing 51% gamma picoline, 36% beta picoline and 13% 2,6-lutidine, parts of 37% formaldehyde solution, 5 parts of boric acid and 1 part of p-tertiary butyl catechol are charged into an autoclave maintained at 200225 C., which temperature is maintained for 45 minutes and then gradually cooled over an hour to 150 C. At this point the reaction is substantially complete and the reaction mixture is cooled after distilling off water and other volatile ingredients at about C.

The crude reaction mixture which constituted methylolated gamma picoline was refluxed with 70% nitric acid, there being approximately twice as much nitric acid as methylolated picolines. After the concentration of nitric acid had dropped to the point at which the reaction slowed down, an additional half part of 100% nitric acid per part of methylolated picoline was slowly added and the mixture refluxed until reaction was complete. Thereupon, volatiles were distilled ofi at C., the dark solution made alkaline, steam distilled to recover unreacted beta picoline and clarified with adsorbent carbon. The clarified solution was then acidified with hydrochloric acid to a pH of about 3.5, whereupon the isonicotinic acid precipitated and was recovered by filtration.

Example 2 A steel bomb was charged with 37% aqueous formaldehyde (50 parts 1.8 moles), commercial mixed picolines (465 parts comprising 235 parts of 4-picoline, 168 parts of 3 picoline and 62 parts of 2,6-lutidine). The bomb was flushed with carbon dioxide gas, and boric acid (5 parts) added. After holding the contents at 300-320 F. for 3 hours, it was removed and used in the following oxidation.

Distillation of an aliquot of the methylolated mixture at mm. resulted in the recovery of all of the 3-picoline, of the 2,6-lutidine and of the 4-picoline. The remaining monomethylolated product was obtained in the range 245260 F. Less than 5% tarry material was collected in the heel.

The methylolated picolines, 100 parts, were added slowly to nitric acid (200 parts) and refluxed for 2 hours after which time 50 parts of nitric acid was added. After four hours more of reflux, the kettle contents were distilled to a pot temperature of made alkaline, and steam distilled to remove unreacted bases. When the clarified (with decolorizing carbon) solution was brought to pH 3.5 with hydrochloric acid, isonicotinic acid was obtained. The pure acid was isolated by filtration, water washing, and then drying.

Example 3 The methylolated picolines, 100 parts, prepared as in Example 1, were added to a mixture of 680 parts of sulfuric acid, 180 parts of nitric acid and parts of sulfur trioxide and added to a little sulfuric acid at 300 C. Upon completion of the addition (1 /2 hours), the oxidation liquors were made alkaline with potash and steam distilled to remove unreacted bases. When the clarified solution was brought to a pH of 3.5 with hydrochloric acid, isonicotinic acid was obtained contaminated with nicotinic acid. The mixture was slurried with two times its weight of hot water and filtered. A high purity isonicotinic acid was obtained.

We claim:

1. A process of preparing isonicotinic acid from a mixture of gamma and beta picoline which comprises (1) reacting the mixed picolines with aqueous formaldehyde to convert the gamma picoline into a methylolated derivative thereof having at least one methylol group attached to the carbon atom of the gamma methyl group thereof and produce a reaction mixture containing beta picoline and a methylolated gamma picoline having the following formula wherein n is an integer from 1 to 3 and m is 3n, (2) heating said mixture with a strongly acid oxidizing agent at a temperature of at least 100 C. until said methylolated gamma picoline is oxidized and converted into isonicotinic acid, the temperature and time of heating being suflicientto convert the said methylolated gamma picoline into isonicotinic acid but insufficient to oxidize any substantial amount of the beta picoline, (3) recovering the unreacted beta picoline, and (4) separately recovering the isonicotinic acid.

2. The process of claim 1 wherein the strongly acid oxidizing agent is nitric acid.

References Cited in the file of this patent UNITED STATES PATENTS 

1. A PROCESS OF PREPARING ISONICOTINIC ACID FROM A MIXTURE OF GAMMA AND BETA PICOLINE WHICH COMPRISES (1) REACTING THE MIXED PICOLINES WITH AQUEOUS FORMALDEHYDE TO CONVERT THE GAMMA PICOLINE INTO A METHYLOLATED DERIVATIVE THEREOF HAVING AT LEAST ONE METHYLOL GROUP ATTACHED TO THE CARBON ATOM OF THE GAMMA METHYL GROUP THEREOF AND PRODUCE A REACTION MIXTURE CONTAINING BETA PICOLINE AND A METHYLOLATED GAMMA PICOLINE HAVING THE FOLLOWING FORMULA 